Power inhaler employing unit doses of powders in pressurized packages

#This invention provides a method for aerosolizing uniform small doses of finely divided substances and more particularly, the invention relates to a technique employing liquefied gases for pressurizing packages of fine pharmaceutical powders which, when ruptured, rapidly disperse the powder into an air stream for inhalation.

#The therapy of lung disease often relies on inhaled medications. Bronchodilators have are widely employed in the treatment of asthma. Inhaled aerosolized antiviral agents are employed in the treatment of infectious diseases. Although most inhaled medications are given for their local effect, there is much recent interest in aerosol delivery of medications for systemic absorption. Inhaled drugs, in the form of very small dry powder particles, may be rapidly and directly absorbed into the blood stream. Thus, for example, proteins and peptides may be self-administered rather than administered by injection.

#The list of drugs currently under investigation for inhalation delivery is quite extensive. Aerosolized insulin for diabetes is anticipated to become a major application of inhalation therapy.

#FIG. 1 shows a flow diagram illustrating material flow.

#FIG. 2 depicts a typical liquefied gas fill line.

#FIG. 3 shows an inhaler employing a pressurized unit dose package.

#The general concept of the finely divided substance packaging process according to the present invention is schematically diagramed in FIG. 1. The finely divided substance filling system consists of a storage cryostat 5 in which the finely divided substance is mixed with a liquefied gas, typically liquid nitrogen, to form a uniform dispersion and stored pending the package fill operation. The liquefied gas is supplied through metering valve 2 from reservoir 1. A finely divided substance source 3 is employed as a reservoir of the finely divided substance that measured out employing metering device 4 for delivery to mixing cryostat 5. Filling line 11 sequentially transports substrates that are to receive a metered dose of dispersed powder under fill nozzle 9. Each metered dose is dispensed under control of metering valve 7. Post filling operations such as liquid medium evaporation, sealing, labeling, etc are carried out at filling line station 13

#This fill system may operate in a batch mode. In this case, a measured quantity of liquefied gas together with a measured quantity of finely divided substance is periodically introduced into cryostat 5. Alternately, continuous feeds may be employed such that a constant volume of the fill mixture is maintained in cryostat 5.

#The liquefied gas reservoir 1 is typically pressurized thus forcing the liquid through metering device 2. The handling and storage of liquefied gases as well as instrumentation for monitoring and controlling flow, temperature, liquid level, etc are well known. The Handbook of Cryogenic Engineering, edited by J. G. Weisend II, published by Taylor & Francis, 1998 describes many of these techniques in detail.